Mechanical Forces Guide Axon Growth through the Nigrostriatal Pathway in an Organotypic Model

Abstract Reconstructing the nigrostriatal pathway is one of the major challenges in cell replacement therapies for Parkinson's disease due to the lack of enabling technologies capable of guiding the reinnervation of dopaminergic precursors transplanted into the substantia nigra toward the striatum. This paper examines nano‐pulling, as a technology to enable the remote manipulation of axonal growth. Specifically, an organotypic model consisting of co‐cultures of the substantia nigra and the striatum is developed to demonstrate that when cortical neural progenitors are transplanted into the substantia nigra, nano‐pulling can guide and enhance the elongation of neural projections toward the striatum. To provide additional evidence, induced pluripotent stem cell‐derived dopaminergic progenitor neurospheres are generated and it is shown that nano‐pulling can induce guided growth and promote the maturation of their neural processes. Altogether, this study demonstrates the potential of nano‐pulling as an emerging technique to promote directed reinnervation within the central nervous system.